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Thoracic Imaging |
1 From the Departments of Radiology (S.D.Q., M.E.H., B.M., O.B., F.B., F.M., P.L.) and Cardiology (T.J, O.D.) and the Intensive Care Unit (A.V.B.), Ambroise Paré Hospital-René Descartes Paris V University, 9 avenue Charles de Gaulle, 92104 Boulogne, France. Received May 6, 1999; revision requested July 16; final revision received February 23, 2000; accepted March 2. Address correspondence to S.D.Q. (e-mail: salah.qanadli@apr.ap-hop-paris.fr)
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Of 204 consecutive patients with clinically suspected acute PE (mean age, 58 years ± 14 [SD]), 158 were enrolled. All patients underwent dual-section helical CT (2.7-mm effective section thickness) and selective pulmonary arteriography within 12 hours of each other. Each image was analyzed independently by two observers, who determined image quality and presence of PE among arterial segments, including at the subsegmental level. The final diagnosis was made with consensus.
RESULTS: Selective pulmonary arteriography was considered optimal in 147 (93%), suboptimal in 10 (6%), and inconclusive in one (0.6%) of 158 patients. Dual-section helical CT findings were considered technically optimal in 140 (89%), suboptimal in 11 (7%), and inconclusive in six (4%). Selective pulmonary arteriography demonstrated PE in 62 patients. Four (6%) of 62 patients had isolated subsegmental PE. The sensitivity of dual-section helical CT was 90%, and the specificity was 94%. The positive and negative predictive values were 90% and 94%, respectively.
CONCLUSION: Dual-section helical CT is an improvement in helical CT that offers a high sensitivity and specificity for the depiction of PE, including at the subsegmental level. Dual-section helical CT can replace pulmonary arteriography for the direct demonstration of PE in a majority of patients.
Index terms: Computed tomography (CT), comparative studies, 60.12112, 60.12115 • Computed tomography (CT), technology • Digital subtraction angiography, comparative studies, 60.1241 • Embolism, pulmonary, 60.721 • Pulmonary angiography, 60.1241
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Several minimally invasive modalities have been used to detect PE. Ventilation-perfusion (V-P) scanning is the most widely used because of its general availability and lower cost (3). Unfortunately, V-P scanning is of limited diagnostic value in approximately 75% of patients who have an intermediate or indeterminate probability of having PE (4–6). Furthermore, in 66% of patients, a definitive diagnosis could not be made by using V-P scanning and clinical data only (7,8). Recently, magnetic resonance imaging (9), electron-beam computed tomography (CT) (10), and helical CT (6,11–18) have demonstrated superiority over V-P scanning as screening tools for acute PE.
Investigators in recent studies (6,13–19) have reported sensitivities and specificities of 53%–100% and 81%–100%, respectively, for helical CT in the detection of PE. In parallel, several investigators (5,6,15,18) have pointed out the limitations of helical CT in the detection of PE in segmental and subsegmental vessels. The poorer efficiency of helical CT for the detection of clots in small vessels has been suggested to be related to limitations in spatial resolution and to the fact that the subsegmental vessels of the upper and lower lobes lie outside the limits of z-axis coverage (9). In most previous studies (6,14,15) in which helical CT was compared with selective pulmonary arteriography, CT was performed by using single–array detector scanners, with 5-mm collimation. Dual-section helical CT (with a double-array detector system) provides wider z-axis coverage when compared with single-section helical CT and reduces the effective section thickness that can be used (20).
Our study was designed to prospectively evaluate, in a large series, dual-section helical CT from the central to the subsegmental vessels in the detection of PE.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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The study was approved by our institutional review board, and informed consent for helical CT was obtained from all 158 patients.
Dual-Section Helical CT Protocol
CT scans were obtained by using a CT Twin Flash scanner (Elscint, Haifa, Israel). This scanner is equipped with a double array of detectors so that, at 5-mm (2 x 2.5-mm) collimation, two contiguous 2.5-mm sections can be obtained, with 1 second per rotation, when dual-section helical CT is performed.
Pulmonary dual-section helical CT was performed by using 120 kV; 199 mA; 5-mm collimation (2 x 2.5 mm); 7.5 mm/sec table speed (pitch, 1.5); 15-cm z-axis coverage; and a 20-second scanning time. Dual-section helical CT was performed in a caudocranial direction. It began at the level of the inferior wall of the right ventricle and ended above the aortic arch for imaging the main, lobar, segmental, and subsegmental arteries of the lower, middle, and upper lobes. Images were reconstructed by using a 180° linear interpolation algorithm, with a standard kernel and a field of view adapted to the patient size. The effective section thickness was 2.7 mm and was reconstructed at 1.3-mm intervals (overlap, 50%).
Contrast material was administered through an 18–21-gauge catheter by using a monophasic bolus injection technique and an automated injector (MCT FLS; Medrad, Rungis, France). Two hundred fifty milligrams of iodine per liter of iodinated contrast agent (iobitridol, Xenetix 250; Guerbet, Aulnay-sous-Bois, France) was used in all patients. A total of 120–150 mL (iodine dose, 30.0–37.5 g) was injected at 4 mL/sec, and the patient was carefully monitored by a nurse. A 10-second injection delay was selected for patients in whom an antecubital venous approach was used. A 12–15-second delay was required for patients with a more distal injection site or with clinical findings suggestive of pulmonary hypertension. No previous timing bolus was used.
CT was performed with a single breath hold in 103 patients (and with a 10-second breath hold in 27 patients, which was followed by quiet breathing). Twenty-eight patients with tachypnea were unable to hold their breath for 10 seconds, so data were obtained during quiet breathing.
Selective Pulmonary Arteriographic Protocol
Pulmonary digital subtraction arteriography (Integris, Philips Medical Systems, the Netherlands, and ADAC, ADAC Laboratories, Milpitas, Calif) was performed in all patients by using a transfemoral venous approach and the Seldinger technique. The right and the left pulmonary arteries were selectively catheterized by using a 6-F Grollman catheter (Cook, Eindhoven, the Netherlands, or Guerbet, Aulnay-sous-Bois, France). Thirty-five to 40 mL of 300 mg of iodine per liter of iodinated contrast material (iobitridol, Xenetix 300; Guerbet) or 320 mg of iodine per liter of iodinated contrast material (ioxalate sodium and ioxaglate meglumine [1:3 ratio], Hexabrix 320; Guerbet) was injected at 15–20 mL/sec. Arteriograms were acquired at five frames per second. Two projections, posteroanterior and oblique, were obtained in each lung. Subselective segmental arteriography was performed when necessary (in 10 patients); the decision to do so was made at the discretion of the investigators. A total of 150–180 mL of contrast material (iodine dose, 45.0–57.6 g) was administered.
Selective pulmonary arteriography was performed first in all patients and was followed by dual-section helical CT within 12 hours, in keeping with the recommendations of our institutional review board.
All patients were monitored for 48 hours after CT.
Data Analysis
CT scans were reviewed at an independent workstation (OmniView or OmniPro, Elscint). All individual native images were analyzed by using mediastinal and lung window settings, with variable levels, at the discretion of the investigator. Images were initially evaluated independently by two investigators (S.D.Q. and O.B.), who were experienced in both helical CT and arteriography, to assess interobserver agreement. These investigators were blinded to the findings of selective pulmonary arteriography. When the two investigators’ results were concordant, the diagnosis was recorded on a study data sheet. Discrepancies between investigators were resolved by a third investigator (B.M.) to establish the final interpretation.
Selective pulmonary arteriograms were reviewed as hard copies and on the computer screen of a digital compact disk archiving workstation (Medical Electronics Vertriebs-GmbH, Wiesbaden, Germany). Arteriograms were reviewed independently by two other investigators (P.L., F.B.), without knowledge of the CT findings. Discrepancies were resolved by a third investigator (F.M.) using the same method as for dual-section helical CT.
Analysis included the evaluation of image quality and the presence of PE. Dual-section helical CT scans were graded as optimal when a high degree of contrast material enhancement was obtained without motion artifacts; as suboptimal when quality was sufficient for analysis of the pulmonary arteries, without a high degree of contrast material enhancement; or as inconclusive when poor opacification or major motion artifacts were observed. The examination was considered inconclusive if at least one segment was nondiagnostic, including at the subsegmental level. In a subgroup of 50 consecutive true-negative CT examinations, the attenuation in A1 and in A10 (according to the nomenclature of the pulmonary arterial branches [21]) was measured retrospectively to evaluate the degree of vessel enhancement during acquisition. Selective pulmonary arteriographic examinations were graded as optimal when all projections were available and acquired during a breath hold, without motion artifacts; as suboptimal when all projections were available, but with motion artifacts, atelectasia, or pleural effusion, or were obtained during quiet breathing; or as inconclusive when arteriograms were of poor quality, incomplete, or insufficient for analysis of all pulmonary vessels. Patients with inconclusive selective pulmonary arteriographic results were excluded from analysis.
The arteriographic criteria defined by Sagel and Greenspan (22) were used to detect PE. An embolism was diagnosed if an intraluminal filling defect or a vessel cutoff at least 2 mm in diameter was seen. The findings were considered negative if two projections (posteroanterior and oblique) did not show PE. The helical CT criteria used in dual-section helical CT to diagnose embolism consisted of direct visualization of an endoluminal nonocclusive thrombus (a central filling defect completely or partially outlined with contrast material) or complete occlusion by a thrombus in a normal-sized or enlarged vessel. No criterion was used to categorize the acute or chronic nature of embolic material.
For the grading of PE, the pulmonary vascular bed was divided into five anatomic arterial levels: first-order (main pulmonary artery), second-order (right and left pulmonary arteries), third-order (lobar and interlobar arteries), fourth-order (segmental arteries), and fifth-order (subsegmental arteries) by using a slightly modified Boyden classification (21) to facilitate CT and selective pulmonary arteriographic analysis and comparison. Anatomic segments were graded as positive, negative, or inconclusive. Examination findings were considered positive if at least one anatomic segment was graded as positive; as negative if all anatomic segments were graded as negative; or as inconclusive if at least one segment was graded as inconclusive, without associated positive segments.
The sensitivity, specificity, and positive and negative predictive values of dual-section helical CT in detecting PE were calculated on a patient diagnosis basis by using selective pulmonary arteriographic findings as the standard of reference. These values were calculated in two ways: by excluding from analysis patients with inconclusive dual-section helical CT findings, and by arbitrarily including patients with inconclusive dual-section helical CT findings to estimate sensitivity and specificity by maximizing the error provided by dual-section helical CT. Inconclusive findings were considered false-negative if selective pulmonary arteriography demonstrated PE and as false-positive if no PE was shown.
Results of attenuation enhancement were presented as the mean plus or minus the SD. Iodine doses administered at each selective pulmonary arteriographic and dual-section helical CT examination and the mean attenuation in A1 and A10 were compared by using the paired t test.
Interobserver reproducibility was assessed by using the 
statistic. Agreement between investigators was classified according to the value as poor (<0.20), fair (0.21–0.40), moderate (0.41–0.60), good (0.61–0.80), very good (0.81–0.90), or excellent (0.91–1.00). A 95% CI, calculated by a standard method, was assigned to the calculated value.
At the end of the study, a joint interpretation session was held for all investigators for a critical analysis of inconclusive dual-section helical CT results and discordant results between dual-section helical CT and selective pulmonary arteriography. The analysis included clinical data, findings of arteriography and venous Doppler ultrasound (US) of the lower extremities in all patients, and findings of the dimerized plasmin fragment D (D-dimer) test, which were available in 101 (64%) of 157 patients. An inconclusive finding in a patient with a low clinical suspicion of PE, without thrombosis at Doppler US and with a negative D-dimer test result, for example, was considered negative.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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A total of 10,833 anatomic arteries (157 first order, 314 second order, 942 third order, 3,140 fourth order, and 6,280 fifth order) were analyzed. Agreement between the two investigators in evaluating image quality was good, with a value of 0.678 (0.404–0.952).
Dual-section helical CT scans were considered optimal in 140 (89%) and suboptimal in 11 (7%) of 157 patients. The value between investigators was 0.565 (0.362–0.768), which corresponded to moderate agreement. Six (4%) patients had inconclusive dual-section helical CT findings because of poor opacification (n = 3), atelectasis and pleural effusion (n = 3), major breathing artifacts (n = 2), or low contrast-to-noise ratios (n = 2). More than one technical factor was observed in three patients. In the subgroup of patients in whom intravascular enhancement was measured, the mean attenuations in A1 and A10 were 340 HU ± 71 and 315 HU ± 55, respectively, without a significant difference. The mean gradient between A1 and A10 was 61 HU ± 35.
A 72-year-old woman experienced anaphylactic shock during dual-section helical CT. Major complications did not occur during selective pulmonary arteriography in the study group. However, two patients were excluded after selective pulmonary arteriography because of an adverse reaction to the contrast media in one patient and pulmonary edema in the other.
The mean iodine dose (33.7 g) injected at dual-section helical CT was significantly lower (P < .05) than that (51.3 g) injected at selective pulmonary arteriography.
Diagnosis of PE
The prevalence of PE at our institution during the study was 36% (in patients 18–75 years of age). In the study population, selective pulmonary arteriography showed PE in 62 (39%) of 157 patients, and 95 patients had normal pulmonary arteries (Table 2). Discordance between the selective pulmonary arteriographic investigators occurred in 17 patients, with a value of 0.781 (0.670–0.892). In 62 patients, 601 PEs were detected (Table 3). The mean number of emboli detected was 9.6 per patient. Fifty-eight (94%) of 62 patients had emboli in central vessels (main, lobar, or segmental arteries) and four (6%) had emboli in only the subsegmental vessels. Most patients (n = 50 [81%]) had multiple emboli. PE was in the lower lobes in 330 (55%) of 601 emboli, in the upper lobes in 195 (32%), and in the middle lobe in 55 (9%).
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value was higher at dual-section helical CT (0.861 [0.781–0.941]) than at selective pulmonary arteriography (0.781 [0.670–0.892]). However, as shown by the confidence interval, the difference did not reach significance. Dual-section helical CT depicted 640 emboli in the 56 true-positive findings. The mean number of emboli depicted was 11.4 per patient. Dual-section helical CT depicted a total of 26 emboli in the second order of pulmonary arteries, while selective pulmonary arteriography depicted 21 emboli at the same level (Table 3). Ninety-two subsegmental emboli were identified at dual-section helical CT (Figs 1, 2), and only 56 were identified at selective pulmonary arteriography.
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Of the three patients with false-negative results, one had isolated subsegmental emboli in the left anterobasal segmental artery that were missed at suboptimal CT (Fig 3). The second patient had a pseudomural defect of the left apical segmental artery that was judged in retrospect as nonindicative of acute PE at selective pulmonary arteriography. The third patient had hypoperfusion of the anterior segment of the left upper lobe at selective pulmonary arteriography, without filling defect or vascular cutoff, that was misinterpreted as PE. In this case, CT showed localized parenchymal hyperlucency with reduced vascular attenuation, and the definitive diagnosis was probably residual hypoperfusion from prior bronchiolitis. Therefore, only one PE at the subsegmental level was really missed at dual-section helical CT.
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No false-positive or false-negative results were observed in patients in whom dual-section helical CT was performed without breath holding. However, two patients from this subgroup had inconclusive CT findings because of major breathing-related artifacts.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Technical Considerations
Our results indicate that dual-section helical CT has a high technical success rate. Dual-section helical CT findings were considered inconclusive in only six (4%) of 157 cases, which is equal or inferior to that reported with helical CT in recent studies. Remy-Jardin et al (23) have demonstrated that 2-mm collimation and a pitch of 2, obtained with subsecond scanning (0.75 second per rotation), which provides an effective section thickness of about 2.7 mm, improved the evaluation of segmental arteries and probably reduced the number of inconclusive CT findings related to inadequate visualization of segmental arteries. They found that the mean number of segmental arteries identified was higher with 2-mm collimation than with 3-mm collimation. In addition, in our study, lymphatic and connective tissue were not considered substantial error factors in image interpretation. Furthermore, no image reformation, as previously reported (24), was required to diagnose PE, probably because of the thin collimation and image overlapping used. In these conditions, pitfalls and interpretative difficulties related to volume averaging are reduced.
Scanning in a caudocranial direction seems to improve the visualization of the lower lobe vessels in which emboli are commonly found, especially in patients unable to hold their breath for more than 10 seconds. However, it is important that CT for the diagnosis of PE include segments of the upper lobes so that relevant PE are not missed. In our experience, 195 (32%) of 601 emboli were in the upper lobes. Two isolated subsegmental PE were in the right and the left apical segments.
PE Diagnosis
The diagnostic value of helical CT in the detection of PE has been reported by several authors in experimental and clinical studies (6,12–19), with variable sensitivity and specificity values. However, to our knowledge, no large series of consecutive patients in which helical CT and selective pulmonary arteriography (the reference standard) were compared have been reported. Our study findings demonstrate that helical CT is useful in establishing the diagnosis of PE in the central vessels. Dual-section helical CT, as compared with single-section helical CT, provides an improvement in spatial resolution (effective section thickness, 2.7 mm) with respect to optimized contrast-to-noise ratio (20). This is supported by our results, with a sensitivity of 97% (56 of 58) and a specificity of 98% (89 of 91) for the diagnosis of PE at the level of the central vessels.
Investigators in recent CT validation studies (6,15,18) and subsequent editorials (5) have pointed out the limitations of helical CT in the detection of PE in the subsegmental vessels (Table 4). Goodman et al (6) compared helical CT with arteriography in 20 patients with an unresolved clinical (abnormal V-P scanning results that were discordant with the level of clinical suspicion) and scintigraphic (intermediate-probability V-P scanning results) diagnosis. Four (36%) of 11 patients who had positive pulmonary arteriograms had isolated subsegmental clots. Only two of these PE were depicted at helical CT, with a sensitivity and specificity of 63% and 89%, respectively. Remy-Jardin et al (14) found four (10%) isolated subsegmental emboli on 39 positive pulmonary arteriograms. Only two of the four emboli were identified on CT scans. van Rossum et al (15) reported three (2%) isolated subsegmental emboli in their 149 patients. However, in that series, 56 patients underwent pulmonary arteriography, and only 15 arteriograms were positive. All three subsegmental emboli were missed at CT. All examinations were performed by using single-section helical CT, with 5-mm collimation and a pitch of 1, 1.7, or 2. As such, the effective section thickness in most cases was greater than 5 mm. In addition, z-axis coverage in most previous studies (6,14,15) was inferior or equal to 12 cm. On the basis of these data, the subsegmental vessels of the upper lobes were clearly not examined in most patients.
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The clinical importance of subsegmental emboli is uncertain (8,14,25,26). If it is admitted that PE as small as subsegmental emboli may be fatal in patients with limited cardiopulmonary reserves, to our knowledge, clinical importance in other patients has yet to be established. Clinical follow-up in the Prospective Investigation of Pulmonary Embolism Diagnosis, or PIOPED, study (4) demonstrated that sequelae of PE did not develop in patients with negative conventional pulmonary arteriograms, even though subsegmental emboli were missed in these patients.
In conclusion, dual-section helical CT is a technical improvement of helical CT and a diagnostic tool with a high sensitivity and specificity for the detection of PE. Our experience indicates that helical CT could replace pulmonary arteriography for the direct demonstration of endoluminal thrombi in the pulmonary arteries in a majority of patients. Selective pulmonary arteriography should be reserved for select patients with an unresolved diagnosis. The evaluation of small vessels, which is improved by thin sections, remains a limitation of current helical CT. However, the development of faster imaging systems (with multisection or multiple-array detectors) with submillimeter isotropic imaging are expected to improve the evaluation of subsegmental pulmonary vessels, with optimal spatial and temporal resolution, in the near future.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, S.D.Q., O.D., P.L.; study concepts, S.D.Q., P.L.; study design, S.D.Q.; definition of intellectual content, S.D.Q., P.L.; literature research, S.D.Q.; clinical studies, S.D.Q., T.J., A.V.B., O.D.; data acquisition, S.D.Q., O.B., F.B., F.M.; data analysis, S.D.Q., M.E.H., B.M., O.B., F.B., F.M., P.L.; statistical analysis, S.D.Q., M.E.H.; manuscript preparation and editing, S.D.Q.; manuscript review, S.D.Q., M.E.H., B.M., P.L.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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